6-Chloro-5-methoxy-nicotinic acid methyl ester

Potassium carbonate (2.59 g, 18.71 mmol) and iodomethane (1.031 mL, 16.55 mmol) were added o a solution of methyl 6-chloro-5-hydroxynicotinate (2.7 g, 14.4 mmol) in N, N-dimethylformamide (40 mL) at room temperature and the resulting mixture was stirred over night. The reaction mixture was partitioned between water and ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate and the solvent was evaporated to give 2.48 g (85percent yield) of the title compound.MS (ESI) m/z 202, 204, 206 [M+1]Potassium carbonate (2.59 g, 18.71 mmol) and iodomethane (1.031 mL, 16.55 mmol) were added o a solution of methyl 6-chloro-5-hydroxynicotinate (2.7 g, 14.4 mmol) in N, N- dimethylformamide (40 mL) at room temperature and the resulting mixture was stirred over night. The reaction mixture was partitioned between water and ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate and the solvent was evaporated to give 2.48 g (85percent yield) of the title compound. MS (ESI) m/z 202, 204, 206 [M+ 1]A mixture of 6-chloro-5-hydroxynicotinic acid methyl ester (1.8 g, 9.6 mmol), methyl iodide (2 M solution in EtTo a solution of methyl 6-chloro-5-hydroxypyridine-3-carboxylate (720 mg, 3.84 mmol) in DMF (10 mL) was added methyl iodide (635 mg, 4.46 mmol) at room temperature. Step 2. Preparation of methyl 6-chloro-5-methoxynicotinate (C6). Potassium carbonate (225 mg, 1 .63 mmol) was added to a solution of methyl 6-chloro-5- hydroxynicotinate (C5) (306 mg, 1 .63 mmol) in acetone (32.6 mL). After addition of methyl iodide (99percent, 0.123 mL, 1.96 mmol), the reaction mixture was stirred at 50 °C for 5 hours. Removal of solvent in vacuo was followed by partitioning of the residue between water (50 mL) and ethyl acetate (50 mL). The organic layer was extracted with ethyl acetate (50 mL) and the combined organic layers were washed with brine (30 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Chromatography on silica (Gradient: 20percent to 80percent ethyl acetate in heptane) afforded the title compound as a white solid. Yield : 202 mg, 1 .00 mmol, 61 percent. LCMS m/z 202.3, 204.3 (M+ 1 ).

Molecular Weight:201.61
XLogP3:1.6
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:201.0192708
Monoisotopic Mass:201.0192708
Topological Polar Surface Area:48.4
Heavy Atom Count:13
Complexity:188
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes